PROJECT SUMMARY/ABSTRACT This award will support mentored training and research needed for Dr. Arjun K. Manrai to transition to an independent investigator position bridging biomedical informatics, cardiovascular medicine, and population health. Throughout this award, Dr. Manrai will be mentored by Drs. Isaac S. Kohane, Joseph Loscalzo, and John P.A. Ioannidis. The long-term goal of Dr. Manrai's research is to improve cardiovascular care and reduce health disparities in multi-ethnic populations. A necessary step towards this goal is to clarify the impact of the ethnicity gap between past studies and current clinical practice. Dr. Manrai's K01 proposed research builds directly off of his previous work in translating clinical genomics across multi-ethnic populations, and includes large-scale analyses of diverse populations (N > 45,000,000) to investigate the appropriateness of existing genetic and clinical criteria for defining pathologic left ventricular hypertrophy (LVH) across different ethnic groups. Dr. Manrai will use heterogeneous datasets (genomic, clinical, and insurance claims data spanning tens of millions of individuals) to clarify the range of normal?and the appropriateness and impact of extant criteria for defining abnormal?molecular and clinical variation in diverse populations. This work will enable Dr. Manrai to: (1) characterize disease risks for genotype variation associated with the inherited heart disease hypertrophic cardiomyopathy (HCM) across ancestrally diverse populations; (2) develop ethnicity-specific phenotype reference ranges for cardiac morphology measures; and (3) measure the related healthcare systems impact using large-scale insurance claims data. In addition to the proposed research, Dr. Manrai will use this award to extend his background in biomedical data science and clinical genomics with extensive, hands-on clinical cardiology training and career development activities. Specifically, Dr. Manrai will: (1) enroll in formal echocardiography training courses and obtain clinical cardiology exposure; (2) attend leading cardiology meetings; (3) obtain training in health disparities and translational research; and (4) increase professional development. As part of his K01 career development activities, Dr. Manrai will work extensively in cardiology clinics around Boston and explore international clinical and research collaborations with clinics in Europe and Africa. This career development award is expected to enable Dr. Manrai to transition to an independent investigator position and lead directly to an R01 research proposal applying the research and training acquired during the award period to study a broader set of diseases of the heart muscle (inherited cardiomyopathies including dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy). Dr. Manrai's K01 proposed research is expected to yield the largest existing catalogue of multi-ethnic cardiac morphology and genetic variation related to LVH. This information will assist physicians, researchers, and patients making decisions with these data daily.